Thousands of unnecessary mastectomies may have resulted among women persuaded to take part in the government’s AgeX study, claims a report by HealthWatch experts published today in the British Medical Journal. The study, announced as “the biggest randomized controlled trial in history”, has already invited over a million women to undergo mammographic screening for breast cancer without first checking they understand the test could harm as well as benefit.
Findings of an eight-year investigation into AgeX by HealthWatch experts and concerned citizens, are published today in an analysis in the British Medical Journal (cite: BMJ 2019;364:l1293 doi:10.1136/bmj.l1293. A full text version can be accessed here). It describes a poorly designed and scrutinized trial which exposes women to foreseeable harm while being unlikely to produce useful data. AgeX randomizes women to receive an extra mammogram on either side of the currently offered 50-70 age range in order to assess the effect on breast cancer mortality. It began in 2009 with an initial target of 1.1 million women. It could continue beyond 2026. Since its inception, evidence has accumulated that mass mammographic screening of healthy women offers little or no benefit, and has substantial harms. But instead of holding back, the trial has only grown in size to an estimated 6 million. Although protests led to better leaflets, women continue to be invited without checks that they understand the risks and that they are taking part in research.
The HealthWatch investigation into AgeX was triggered in 2011 when medical writer Mitzi Blennerhassett deduced from some small print that a screening invitation she received at age 72 was not routine but part of a clinical trial. Knowing that international ethical standards for human experiments say that participants must be told that they are in a trial and given details of benefits and harms in language they can understand, she decided to find out more. Her letters to NHS departments received either cursory replies or contradictory information. Over the following years she was joined by Susan Bewley (emeritus professor of obstetrics and women’s health, Kings College London, and HealthWatch trustee) and Mandy Payne (freelance editor of the HealthWatch Newsletter). They found:
- It took three freedom of information requests to obtain the study protocol that was barely 7 pages long*.
- The triallists had specified from the outset that informed consent would not be sought, i.e., there would be no explicit check that women presenting for screening fully understood the risks.
- The Principal Investigator of the study is not a scientist or doctor, but has a degree in Ancient History and Classical Civilisation and her medical doctorate and professorship are both honorary.
- The proposed trial was implemented without having been properly peer-reviewed. Instead of receiving independent academic and scientific scrutiny it was passed by an internal Department of Health committee.
- No body appears to admit full responsibility for the scientific content and oversight of the trial. In responses to letters inquiring on this question, it seems to be passed around between the AgeX investigators, the sponsor (Oxford University), and the Research Ethics Committee (REC).
How can mammograms harm women? Many “positive” screens result from discovery of tiny, microscopic tumours that will never grow, or grow so slowly that they would not have gone on to harm a woman in her lifetime. However, once detected, this is followed by surgery or radiation. The tests and diagnoses cause fear and anxiety. Cancer treatments are highly toxic, and may cause pain, disfigurement and even trigger new cancers. Some women are harmed who would have remained healthy but for the screening. At best, the woman survives a frightening diagnosis and “lives with cancer” for the rest of her life. Screening has not been shown to save lives when all-cause mortality is considered, and it increases the chance of mastectomy. It has not been shown to reduce the most advanced and aggressive cancers. Fortunately, today’s treatments for breast cancer are much better than forty years ago, and most women diagnosed via symptoms have effective treatment.
Lead author Susan Bewley says “Good researchers would welcome openness and scrutiny. We call on scientists and researchers worldwide to examine the detail and judge the value of this enormous trial that was not competitively funded, nor properly peer reviewed, which has a changing rationale, protocol and endpoints, and which does not seek explicit informed consent from the ever-growing number of women recruited.”
Commenting on the BMJ paper, leading breast cancer surgeon and researcher Professor Michael Baum, who was one of the original architects of the breast screening programme, but who now believes it does more harm than good, said “Whilst the world’s scientific community has woken up to the fact that screening for breast cancer does not save lives or for that matter save breasts, the monstrous AgeX trial is recruiting over 6,000,000 women to an RCT to extend the age group for screening to 47-79. The cost to the exchequer is huge, never mind the cost of managing the physical and psychological outcomes of over-diagnosed cases. This paper by Bewley, Blennerhassett and Payne is timely and AgeX should be shut down. The hubris of the non-clinical epidemiologists running this study, who never have to look a woman in the eye after a ‘positive’ mammogram, is unspeakable.”
The authors of the BMJ paper call for an inquiry into the research governance gaps that this investigation has exposed. Further information on the trial, including documents obtained as a result of freedom of information requests, are now available on the HealthWatch website in a detailed update.
HealthWatch, in common with many international experts, believes the evidence does not support benefit of mass mammographic screening of symptom-free average-risk women. However, women at high risk, e.g. with a family history of breast cancer, DO benefit from close monitoring. Any women with breast symptoms should seek medical advice as soon as possible.
Some key facts and numbers:
- 2009 – the trial of extending the age range for breast screening in England begins
- 2011 – the existence of the trial of extending the age range for breast screening in England is announced publicly, in response to a public letter in BMJ from Susan Bewley to the Cancer ‘tsar’ Mike Richards
- 2016 – the protocol for the AgeX trial is finally made freely available online for the general public – by now it is in at least its 4th iteration in operation
- 50-70 – the standard age range offered breast screening currently by NHS
- 47-49, and 71-79 – extra age ranges in AgeX
- 7 – the number of pages in the original AgeX trial protocol
- 2 – the number of scientific references in the original AgeX trial protocol
- 3 – the number of freedom of information requests made before the original protocol was released to HealthWatch investigators, in 2014
- 1 million – the original target for the number of women to be included in the study
- 6 million – the current new target number of individual women proposed to be included in the study (to include participants and unscreened controls)
- 1 million – the number of women who had, by end of 2016, received an extra mammogram as part of AgeX
- 1 in 10 – the chance of a woman aged 50+, who takes part in the standard breast screening programme over the course of 11 years,** having a false alarm after a mammogram and unnecessarily having additional testing or tissue removed (biopsy)
- 1 in 200 – the chance of a woman aged 50+, who takes part in the standard breast screening programme over the course of 11 years,** unnecessarily having partial or complete removal of a breast
- 22 in 1000 – the risk of dying of cancer for a woman aged 50+ over the course of 11 years regardless of whether or not she attends standard breast screening**
*A protocol is the detailed “recipe” for how a clinical trial is conducted - protocols are commonly 50-200 pages of dense and highly detailed text that has been written and checked many times. The NHS Health Research Authority website encourages researchers to make protocols publicly available in the interests of transparency https://www.hra.nhs.uk/planning-and-improving-research/research-planning/protocol/